Characterization of Sex Differences in the Reinforcing Effects of Nicotine

Abstract

It is presently unclear whether ovarian hormones, such as estradiol (E2) promote the reinforcing effects of nicotine in females. Thus, we compared extended access to nicotine intravenous self-administration (IVSA) in intact male, intact female, and OVX female rats (Study 1) as well as OVX females that received vehicle or E2 supplementation (Study 2). The E2 supplementation procedure involved a 4-day procedure involving 2 days of vehicle administration and 2 days of E2 administration. Two doses of E2 (25 or 250 ug) were assessed in separate groups of OVX females in order to examine the dose-dependent effects of this hormone on the reinforcing effects of nicotine. The rats were given 23-hour access to nicotine IVSA using an escalating dose regimen (0.015, 0.03, and 0.06 mg/kg/0.1 ml). Each dose was self-administered for 4 days with 3 intervening days of nicotine abstinence. The results revealed that intact females displayed higher levels of nicotine intake as compared to males. Also, intact females displayed higher levels of nicotine intake versus OVX females. Lastly, our results revealed that OVX rats that received E2 supplementation displayed a dose-dependent increase in nicotine intake as compared to OVX rats that received vehicle. Together, our results suggest that the reinforcing effects of nicotine are enhanced in female rats via the presence of the ovarian hormone, E2.